Tachykinin is a general name for a group of peptides having similar structures and, in mammals, substance P(SP), neurokinin A (NKA) and neurokinin B (NKB) are representative ones. They are neuropeptides widely distributed in living bodies and the substance where the physiological function was most specifically studied is a substance P. The substance P is a peptide comprising 11 amino acids and showing hypotensive action, contracting action for smooth muscles, promoting action for secretion of saliva, exciting action for neurons, inducing action for pain reaction. It has been known to be related to various diseases such as digestive disease, neulogic disease, respiratory disease, and has been suggested to deeply participate particularly in inflammation, allergy, carcinoid syndrome, chronic pain, headache, Crohn's disease, depression, nausea, etc. Accordingly, an antagonist to tachykinin such as the substance P is useful as pharmaceuticals such as an anti-inflammatory agent, an agent for allergic diseases, an analgesic, an antiemetic, an agent for irritable bowel syndrome, an agent for skin diseases, an agent for vasospastic diseases, an agent for cerebral ischemic diseases, an antidepressant, an antianxiety agent, an agent for autoimmune diseases, a muscle relaxant and an antispasmodic.
Various anti-tachykinin compounds have been developed and reported with a purpose of developing the therapeutic agents for the above mentioned diseases in which tachykinin participates. However, there are problems in their pharmacokinetics such as a undesirable transfer into the blood and their safety whereby anti-tachykinin compounds having novel structures have been demanded. For example, in the Non-Patent Document 1, benzyloxyphenethylpiperazine derivatives in which a partial structure thereof is similar to the structure of the compounds of the present invention are reported. However they are the compounds having a clearly different structure from the benzyloxypropylamine derivatives of the present invention which are linear molecule without piperazine skeleton.
Non-Patent Document 1: Bioorganic & Medicinal Chemistry Letters, vol. 13, pages 437 to 442 (2003)